Allergy and parasites Flashcards
What is a hypersensitivity reaction?
A persistent immune response in the absence of a true pathogen, causing inappropriate response that is detrimental to host. Usually in response to innocuous allergens.
What is a type I sensitivity reaction?
IgE mediated mast cell degranulation and eosinophil activation = Allergy IgE response
Usually against food, drug, venom, hayfever, anaphlaxis
What is a type II sensitivity reaction?
IgG autoantibody damaging self cells = AI / cytotoxic IgG
Causes AI haemolytic anaemia, myasthenia gravis, Goodpasture’s, idiopathic thrombocytopenia purpura.
What is a type III sensitivity reaction?
IgG - antigen immune complex damage = immune complex disease
Causes serum sickness, arthus reaction, SLE, cryoglobulinaemia.
What is a type IV sensitivity reaction?
T cell mediated cellular response = Delayed hypersensitivity.
Causes contact dermatitis, delayed drug reaction, mantoux test
What is the difference between type I and IV?
Type I is immediated, within minutes, and life threatening. The cause is easily identified.
Type IV occurs >4hrs after antigen exposure due to T cell migration.
What tests are used to identify allergen of type I reaction?
IgE skin prick - allergen pricked into skin. Causes reaction within 10 minutes as the mast cells lie underneath the skin. Only shows sensitisation so requires Pt clinical and temporal Hx to confirm.
Serum testing.
What test can be used to identify the allergen of a type IV reaction?
Patch testing - On removal of the patch, if the rash fades it is an irritant but if the rash continues to get worse over 5 days it is an allergen inducing IV.
What other types of reactions may occur that are not allergies?
Irritant response to a burn or chemical.
Food intolerance
Side effect to a drug
Why is it possible to develop allergies throughout life?
Allergies only develop on 2nd exposure, once the immune system has been sensitised to the allergen.
What induces Ig class switching in type I reaction?
Th2 cells produce IL-4 and IL-13 to trigger IgE switching.
What inhibits class switching?
Production of IFNgamma by Th1 cells
Why does class switching sensitise the Pt to an allergen?
Class switching produces long term memory so on re-exposure the allergen induces the IgE mediated response.
Define atopic.
The genetic tendency to develop allergic disease due to predisposition e.g. polymorphism in IL-4 R or FCeR1. At increased risk of asthma, dermatitis, rhinitis and multiple allergies.
What is the hygiene hypothesis?
Exposure to bacteria and viruses in early life reduces the risk of developing an allergy by skewing the immune system towards Th1 response.
Describe the stages involved in an IgE mediated response?
1) A specific IgE recognises an allergen
2) The extra constant region of IgE bind with high affinity to the IgE-allergen complex to effector cells via FCeR1.
3) Mainly binds to mast cells in tissue and basophils in the circulation.
4) The cross linking causes degranulation.
5) Induces the acute phase response upon release of preformed mediators.
What are the symptoms associated with an allergic acute phase response and why do they occur?
Hypotension - vasodilation
Confusion - reduced cerebral blood flow
GI symptoms - smooth muscle contraction
Tachycardia - reduced resistance and coronary blood flow
Bronchospasm - bronchoconstriction
Angioedema - vascular permeability
Hives/urticarial - histamine and bradykinin
Which mast cell mediators are released in the early phase?
Preformed: Histamine = vascular permeability Kallikrein = activates bradykinin for vasodilation serotonin = smooth muscle contraction proteases = irritates nerve endings
Which mediator can be used to diagnose anaphylaxis and why?
Tryptase as it is the only mediator that lasts 8 hours, all the others are short acting.
Which mast cell mediators are released in the late phase and why?
Newly synthesised: PGs Cytokines Leukotrienes Needed to escalate the response through cell recruitment.
What is a biphasic reaction and why does it occur?
Late phase mediators are released 6-8 hours after the initial response is treated, causing an escalated response hours after the initial.
How is a biphasic reaction prevented?
Steroids and Antihistamine
What is anaphylaxis?
A severe, life-threatening hypersensitivity response, characteristed by a dramatic fall in BP and severe airway constriction (bronchoconstriction or laryngeal oedema). Caused by wide spread vasodilation due to spread of mediators in the circulation.
Why is anaphylaxis commonly undiagnosed?
Hives, skin changes and angioedema are not present in 20% of cases and leads to diagnosis of asthma.
How is anaphylaxis treated?
Immediate IM adrenaline. Has short half life so can be given every 5 minutes if no improvement seen.
- 3mg adult and 0.15mg child in community.
- 5mg adult and 0.01mg per kg child in hospital
Why is the dose of adrenaline in the community lower than in a hospital and why is it given IM?
Due to pro-arhythmic action
What is a mast cell and its function?
Located in tissues to respond to allergy be releasing histamine. TNFalpha, IL-4 and IL-5 are also released to trigger the cascade.
What are basophils?
Circulating mast cells that release histamine, IL-4, IL-13. Can travel to lymph nodes for priming IgE class switching.
What are eosinophils and where are they found?
Circulate in blood and migrate into the tissue via chemokines. Production in BM is stimulated by IL-5. Involved in anti-helminth immunity and allergy by releasing mediators from their lysosomal granules.
What immune mechanism is involved in anti-helminth immunity?
IgE mediated degranulation upon recognition by mast cells. Helminth are too big for phagocytosis.
What is the IgE response to a helminth?
1) Mast cells detect helminth via IgE and release cytokines.
2) IL-5 is released from mast cells to mobilise eosinophils to helminth.
3) Eosinophil attaches to the helminth via FCeR1 region of IgG and IgE .
4) High binding affinity releases contents from lysosomal granules.
Which mediators are produced by eosinophils?
MBP (major basic protein) - strong alkali
Ribonucleases, peroxidase, proteases
ROS and nitrogen radicals
Why might tissue damage occur as a result of eosinophil immune response?
Mast cells release eosinophil chemotactic factor causing eosinophils to accumulate and release mediators within tissues causing damage e.g. lung damage in asthma Pts.
How is the helminth eradicated after it has been killed by eosinophils?
IL-13 production from eosinophils causes goblet cell hyperplasia and increased mucus production helping to pass helminth through the GIT. Also stimulates contraction of GIT smooth muscle.
Also affects lungs so may get bronchoconstriction.
